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PMID: 22358332 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

PI3K signalling: the path to discovery and understanding.

Nature reviews. Molecular cell biology ·Vol. 13 ·No. 3 ·2012-00-23 ·Pages 195-203

Vanhaesebroeck B, Stephens L, Hawkins P

Abstract

Over the past two decades, our understanding of phospoinositide 3-kinases (PI3Ks) has progressed from the identification of an enzymatic activity associated with growth factors, GPCRs and certain oncogene products to a disease target in cancer and inflammation, with PI3K inhibitors currently in clinical trials. Elucidation of PI3K-dependent networks led to the discovery of the phosphoinositide-binding PH, PX and FYVE domains as conduits of intracellular lipid signalling, the determination of the molecular function of the tumour suppressor PTEN and the identification of AKT and mTOR protein kinases as key regulators of cell growth. Here we look back at the main discoveries that shaped the PI3K field.

MeSH Terms
Animals Antineoplastic Agents/pharmacology,therapeutic use Clinical Trials as Topic Enzyme Inhibitors/pharmacology,therapeutic use Humans Neoplasms/drug therapy,enzymology Phosphatidylinositol 3-Kinases/chemistry,metabolism Phosphoinositide-3 Kinase Inhibitors Phosphorylation Protein Structure, Tertiary Proto-Oncogene Proteins c-akt/metabolism Signal Transduction
Chemicals
Antineoplastic Agents Enzyme Inhibitors Phosphoinositide-3 Kinase Inhibitors Proto-Oncogene Proteins c-akt
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Vanhaesebroeck Bart
Centre for Cell Signalling, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom. bart.vanh@qmul.ac.uk
Stephens Len
Hawkins Phillip
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Article Info
Journal
Nature reviews. Molecular cell biology
Abbr.
Nat Rev Mol Cell Biol
ISSN
1471-0080
DOI
10.1038/nrm3290
Email
bart.vanh@qmul.ac.uk
Published
2012-00-23
Epub
2012-00-23
Pages
195-203
Language
English
Region
England
NLM ID
100962782
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · BBS/E/B/000C0413 · United Kingdom
Cancer Research UK · C23338/A10200 · United Kingdom
Wellcome Trust · WT 085,889 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/I007806/1 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBI003916/1 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBS/E/B/0000H235 · United Kingdom
Biotechnology and Biological Sciences Research Council · BB/I008489/1 · United Kingdom
External Links
PubMed source DOI: 10.1038/nrm3290 View journal details
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